martedì 10 aprile 2012

The Weak Link Between GcMAF and HIV infection. A Broken Arrow in the AIDS Denialists’ Quiver.

Guido Poli,
director of the AIDS Immunopathogenesis Unit at the San Raffaele Hospital and Professor
of Pathology, School of Medicine, of the Vita-Salute San Raffaele University in
Milano, wrote a paper for SIMIT (Società Italiana di Malattie Infettive eTropicali)on GcMAF, HIV infection and
Professor Ruggiero’s team research.

The paper
is accessible only to the physicians members of SIMIT, but Professor Poli gave us the authorization to spread it even to non-infectious diseases experts.

The Weak Link Between GcMAF and HIV infection. A Broken Arrow in the AIDS
Denialists’ Quiver.

At the recent ICAR meeting held in Florence, March 2011, a poster
presented by Gabriele Morucci and Tiziana Punzi of the University of Florence,
Italy, discussing “Effect of Cadmium and Gc-Macrophage Activating Factor
(Gc-MAF) on Intracellular HIV Targets in Normal and Transformed Human Breast
Cells” has raised the voice and enthusiasm of so-called AIDS denialists, i.e.
individuals not acknowledging the etiology of AIDS in the infection by the
human immunodeficiency virus (HIV) 1. Not as much for the
scientific content of their poster, as later discussed,but for incorporating in
their conclusions the sentence: “Our data….provide experimental evidence for
the words “Our immune system will get rid of the virus within a few weeks, if you have a good immune system”, thus reversing
the longassumed cause-effect relationship between HIV and AIDS.” The poster is now displayed in the web site of the Gc-MAF producing
company in support of their market to use this molecule to cure “cancer,
AIDS and immune diseases”. Here we will revise what is known on Gc-MAF
effects on HIV infection in vitro and in vivo.

The first consideration is that in the era of recombinant technology
that has allowed the sequencing of the human genome it is unusual that a
“relevant” biological activity described in 1987 (by the same group now
claiming its efficacy against HIV infection 2) has not lead to identification of a
specific gene and related protein. The term “MAF” was commonly used in the ‘70s
and it has been essentially abandoned in the field after the demonstration of
its identity with interferon-γ (IFN-γ), indeed a main “macrophage activating
factor” 3. A paper identifying a MAF distinct from IFN- γ was published in 1988 4, but did not have follow-up. Of course, IFN-γ is not the only “macrophage
activating factor” since this function can be exerted by several cytokines, chemokines and factors of non-proteic nature such as
prostaglandins and leukotriens.

Second, the “key reference” paper cited by the authors in their poster
was published in 2009 5. Almost all references related to GcMAF
cited in the paper are self-referred (i.e. they refer to publications by the
same group of investigators), a very suspicious indicator of the relevance of
the “discoveries” described in the papers. A more technical analysis of their
published data reveal the adoption of questionable methodologies to approach a
monumental issue such as “viral eradication”, including the use of a cell
line-based culture method to determine “the viral load in patient plasma” rather
then sensitive PCR-based methods (or equivalents); also when RT-PCR was adopted
its cut-off was 400 copies/ml, a standard clearly obsolete in comparison to the
common standard of 50 copies or less in use by several years. The implication
that “administration of GcMAF normalized the levels of Nagalase activity (an
enzyme that, according to the authors, deglycosylate the MAF precursor leading to
inactivation of MAF and it is upregulated by HIV infection and “it is an
intrinsic component of the envelope protein gp120”) to those of healthy
controls, indicating eradication of HIV-infection” is so evidently unproven
that the reviewers and the Editor of the Journal of Medical Virology (IF: 2,47)
should have required its elimination for the broad implication that such a
sentence could have implied. Indeed, the same sentence has been indeed
incorporated in the Introduction of the poster by Morucci and Punzi: “Thus,
it was demonstrated that GcMAF eradicates HIV infection in asymptomatic
HIV-infected patients 5, and here we report for the first time
its effects in full-blown AIDS patients (BOX 1).”

This poster Box 1 summarizes the features of two AIDS patients that have
spontaneously decided to assume GcMAF. Case report 1 describes the case of a patient
resistant to “conventional ARV” (not specified) who experienced a gain in CD4+ cell counts (from 40 to 298 cells/ml –
likely meaning “μl”…) and reduction of viremia from 160,000
to 2,343 copies/ml after 10 weeks of suspension of the conventional ARV therapy
and assumption of GcMAF by intramuscular injection with improvement of general
conditions including peripheral neuropathic pain and limb stiffness. The second
case report describes the events occurring in another AIDS patient who, after
the third injection of GcMAF after HAART suspension experienced significant
systemic inflammatory symptoms following GcMAF injection (flushes, diffused
muscle pain, high fever, headache, etc.) relieved by assumption of an
antiinflammatory agent. The only additional information provided is that “ever
since the patient reports constant improving of her general conditions.” for
which the authors astonishingly conclude that “These side effects, although
unwelcomed, appear to demonstrate that GcMAF actually induces immune system
reconstitution.” Clearly, these two cases do not allow any inference on the
efficacy of GcMAF on HIV replication in vivo, since the amelioration of
general conditions, the improvement of CD4+ cell counts and reduction (in any case, not eradication!) of viremia in
a multidrug experienced patients, although of interest, could be the result of
multiple variables not reported in the summary. The second case description
strikes for lack of clinical data (viremia? CD4 cell counts?) and raises the
concern that GcMAF could induce systemic inflammatory reactions and not “immune
reconstitution effects” as incomprehensibly interpreted by the authors. The
remainder of the poster describes activating/differentiating effects on a
breast cancer cell line (MCF-7) and on a mononuclear phagocyte cell line
(MonoMac 6) in response to GcMAF, results that are clearly not related to HIV
infection and to the final claim of the authors.

In conclusion, the anecdotal use of GcMAF in HIV infected individuals
does not gain any scientific support by the present poster and should not be
encouraged by the medical community. On the contrary, the information, based on
the present report, that GcMAF may induce a systemic inflammatory syndrome
should be communicated to the medical community to further discourage its
“experimental” use in HIV infected individuals.

This conclusion is in line with the comment of the
journal Medical Hypothesis that decided to withdraw a paper by the team to
which the authors of this poster belong: “This Article-in-Press has been
permanently withdrawn. The editorial policy of Medical Hypotheses makes it
clear that the journal considers "radical, speculative, and non-mainstream scientific
ideas", and articles will only be acceptable if they are "coherent
and clearly expressed." However, we received serious expressions of
concern about the quality of this article. Given these important signals of
concern, we commissioned an external expert panel to investigate the
circumstances in which this article came to be published online. The panel
recommended that the article should be externally peer-reviewed. Following a peer-review
process managed by The Lancet editorial team, all five external reviewers recommended
rejection, as a result of which the expert panel recommended permanent
withdrawal. The Publisher apologizes for any inconvenience this may cause. The
full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
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